In industries such as food, feed, agriculture, drug, animal drug, personal care, skin care, etc., the use of certain ingredients or extracts is difficult since their constituent materials have low or poor solubility in water, which leads to low stability, accessibility, availability, or bioavailability. Examples of such ingredients, synthetic compounds, or extracts can include phenolic compounds (e.g., flavonoids, curcuminoids), carotenoids, and active pharmaceutical ingredients (APIs, e.g., drugs), as well as raw or purified extracts from herbs, microbes and animals.
For drugs administered via oral route, drugs must be dissolved for the molecules to permeate through cell membranes to reach the systemic circulation. The solubility and permeability of drug are largely affected by their physicochemical properties. In addition to neutral drugs (e.g. griseofulvin), a large number of drug compounds are either weak acids (e.g. ibuprofen) or bases (e.g. itraconazole). For these drugs, their un-ionized and ionized forms in water affect their solubility and permeability. Along the GI tract, the small intestine provides the largest surface area for drug absorption, and its membranes are more permeable than those in the stomach. In general, the intestinal pH (5-7) affects the solubility of drugs and their membrane permeability. For weak acids, their solubility is improved due to ionization; for weak bases, their solubility is reduced due to un-ionization.
It is estimated that roughly 40% of new drug molecules present drug delivery challenges due to their low solubility. The Biopharmaceutics Classification System (BCS) was developed as a systematic approach to classify Active Pharmaceutical Ingredients (APIs) based on their solubility and permeability. Based on the BCS, drug solubilization is necessary for the delivery of compounds in Class II (low solubility, high permeability) and Class IV (low solubility, low permeability). In particular, compounds in Class II, such as griseofulvin, make the group for which the solubilization technologies can readily solve the drug delivery problem.
Accordingly, there are different approaches for addressing the solubility issue of active ingredients (AIs), such as nanoemulsions, dendrimers, block copolymer micelles, cocrystal formation, and amorphous dispersions. The amorphous dispersion approach has drawn great interest in drug formulation due to several reasons. First, it has the potential to eliminate the solubility limitations imposed by the thermodynamic stability of crystal lattice. Second, by the action of polymer matrix it is possible to induce supersaturation over time scales comparable to those required for systemic absorption.
One particular example of such ingredients or extracts includes phenolic compounds, such as quercetin and curcumin. Quercetin and curcumin are strong antioxidants and have anti-inflammatory, antiviral, and anti-cancer effects. In particular, curcumin is a potent anti-cancer drug that can be used clinically. However, their low solubility prohibits their use in food, nutraceutical, cosmetic, and medical formulations. To address this problem, a variety of techniques have been employed to improve the water-solubility of such low or non-soluble phenolic compounds. For example, it has been proposed to improve the solubility or bioavailability of curcumin using specific compounds (e.g., piperine), polymeric nanoparticle encapsulation, or surfactant micelles. However, these methods are expensive and/or have limited capability to solubilize phenolic compounds. In addition, some of these strategies are simply ineffective.
Poor water solubility of some active pharmaceutical ingredients (APIs), such as a number of drugs is one of the major problems in drug formulation and drug absorption. Systems to improve the water solubility of these drugs are essential for their bioavailability. For example, application of paclitaxel in cancer therapy has been limited by its low water solubility, and current practice of dissolving paclitaxel usually leads to short-term physical stability with quick precipitation of drug molecules. To enhance paclitaxel solubility and physical stability, solvents have been used to disperse drug molecules. To be effective, however, the concentration of solvents needs to be very high, which may lead to difficulties in formulation and administration.
Another example is ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), and a core medicine in the WHO Model List of Essential Medicines. It is broadly used to relieve symptoms of arthritis and fever and as an analgesic where there is an inflammatory component and dysmenorrhea. Ibuprofen belongs to Biopharmaceutics Classification System (BCS) class II, for which the rate of drug dissolution or drug solubility is the rate-limiting step in the absorption.
Another example is griseofulvin. Griseofulvin is a widely used antifungal drug in the treatment of mycotic diseases of skin, hair and nails. Griseofulvin is poorly soluble in water and has been used as a standard in the research to increase drug bioavailability.
Another example is itraconazole. Itraconazole is an orally active triazole antimycotic agent and has been used to treat various fungal infections including histoplasmosis, blastomycosis and oncomycosis. It is a weakly base drug with poor water solubility.
Other examples are aripiprazole, celecoxib, imatinib, ezetimibe, modafinil, dutasteride, ciclosporin, darunavir, raloxifene, olmesartan, and cinacalcet. Their low solubility affects their efficacy at various levels.
Similar issues persist in industries related to the extraction and formulation of medicinal, nutritional, or functional materials from plant, microbial, or animal organisms, such as herbal extracts, Chinese medicine, and colorants. In such industries, there are a number of extraction processes, including: (1) aqueous extraction; (2) solvent-based extraction, and (3) supercritical fluid extraction. In many circumstances, the solute compound (or materials) has low water solubility, which makes it difficult to formulate as a product. Additionally, in industries related to feed, animal drugs, personal care, cosmetics, paints, pesticides, herbicides, or other food and non-food areas, the low solubility of certain materials in products is the source of numerous difficulties in formulation, processing and/or the function of such products.